There is a severe shortage of cadaveric organs for liver transplant. Critically ill patients compete with one another for the only therapy open to them. Only new supplies of organs or alternative therapies can address this need. The proposed research seeks to develop a model of the liver allocation system to evaluate the costs, effectivenesses and systemic implications of non-cadaveric organ replacement technologies (ORT). Using discrete event simulation (DES), the liver allocation system with and without ORTs will be modeled. DES is a modeling technique that explicitly captures the competition for limited resources, which is central to this problem. We will develop a model to estimate the health and economic effects of introducing new therapies such as tissue-engineered organs, xenotransplants, living-donor partial-liver transplants, and liver dialysis. Outcomes will include costs, quality-adjusted life-years and process measures such as waiting time and resource utilization. The model will also be used to identify performance characteristics required to make ORTs useful alternatives to cadaveric organs and help design future trials by identifying parameters which influence outcome and are not know with certainty. Finally, the model will help estimate the effects of gaming by patients and institutions and help predict the way ORTs will change the decision-making environment. Data from diverse sources such as the Optimal Timing of Liver Transplant project, UNOS and NIDDK and others will be used to derive parameter estimates for the models. Estimates of functionality, longevity, and time to production for ORTs will be derived from the literature and expert opinion. The candidate has previously developed and verified a model of the current liver allocation system. This model will be expanded and used to examine the following specific aims: 1) determine the role and cost-effectiveness of organ replacement therapies (ORT) that are functionally equivalent to cadaveric organs; 2) determine the role and cost-effectiveness of ORTs that are temporary or not as effective as cadaveric organ; 3) examine liver allocation policy with/without ORTs from the perspective of game theory and ethics. On completion, this project should contribute to the general knowledge of the liver allocation problem and help policy makers better understand which technologies are the best investments. The research will lay the groundwork for future R01 proposals by the candidate.